1. Field
Provided is biomarker TFF1 for predicting and/or monitoring an effect of a c-Met inhibitor, a composition for predicting an effect of a c-Met inhibitor and/or selecting a subject for application of a c-Met inhibitor including a TFF1 detecting substance, a composition for monitoring an effect of a c-Met inhibitor including a TFF1 detecting substance, a method of predicting an effect of a c-Met inhibitor and/or selecting a subject for application of a c-Met inhibitor using TFF1, a method of monitoring an effect of a c-Met inhibitor using TFF1, and a method of treating and/or preventing cancer including administering a c-Met inhibitor to the selected subject.
2. Description of the Related Art
A biomarker generally refers to a measured characteristic which may be used as an indicator of some change caused in an organism by an external factor. Active studies have recently been made to apply biomarkers to the diagnosis of diseases, such as cancer, stroke, dementia, etc., and the prediction or monitoring of therapeutic effects of some agents. Among biomarkers relevant to drug development are pharmacodynamic markers (PD markers) for indicating whether drugs are functionally effective in vivo, and predictive markers for indicating the likely responsiveness to particular drugs before administration. The use of such markers is helpful in establishing the clinical strategy of drugs. For example, a predictive marker, designed to indicate sensitivity or resistance to drug action, may be applied to the selection of patients to allow for more effective drug therapy while the action mode of a drug in individual patients can be monitored with a pharmacodynamic marker, which together can lead to the establishment of effective therapeutic strategies. Further, even in the absence of a predictive marker, a pharmacodynamic marker permits the early monitoring of responses to a drug, thus discriminating a drug-effective group from a drug-ineffective group in an early stage. Consequentially, more effective and successful drug therapies can be established. In addition, when applied to the monitoring of responsiveness to a drug as a function of concentration, a pharmacodynamic marker can be an index for calculating suitable doses of the drug.
To date, cancer is one of the leading causes of death. Although the development of medical techniques has brought about a remarkable progress in cancer therapy, the 5-year survival rate has only improved by 10% over the past two decades. This is because cancer characteristics, such as rapid growth, metastasis, etc., make it difficult to diagnose and treat within a suitable time. The introduction of suitable biomarkers to cancer therapy would identify the characteristics of cancer to increase the opportunity of applying a suitable therapeutic in an optimal time, whereby cancer treatment could reach high success rates. For example, patients with lung cancer may differ from each other in cancer classification, genotype, and protein secretion, and thus must be treated with different, proper therapeutics. For chemotherapy using a specific drug, a corresponding biomarker, if present, would reduce the number of erroneous trials and increase possibility of success. In this regard, it is very important to explore biomarkers for predicting or monitoring the effect of anti-cancer therapeutics. A proper biomarker, if successfully exploited, can make a great contribution to the utility and value of anti-cancer drugs and the success rate of treatment with them.
c-Met is a hepatocyte growth factor (HGF) receptor. Hepatocyte growth factor (HGF) acts as a multi-functional cytokine which binds to the extracellular domain of the c-Met receptor to regulate cell division, cell motility, and morphogenesis in various normal and tumor cells. The c-Met receptor is a membrane receptor that possesses tyrosine kinase activity. c-Met is a proto-oncogene, per se, that encodes the representative receptor tyrosine kinase. Occasionally, it takes part in a variety of mechanisms responsible for the development of cancer, such as oncogenesis, cancer metastasis, the migration and invasion of cancer cells, angiogenesis, etc., irrespectively of the ligand HGF, and thus has attracted intensive attention as a target for anti-cancer therapy. Actually, targeted therapies, such as antibodies against c-Met, have been continuously developed.
A therapy with a developed c-Met targeting drug might be more effective treating cancer, with an elevated probability of success if there is a biomarker that is capable of predicting and monitoring the therapeutic effect of the drug to select patients suitable for the drug therapy and to monitor patient responses to the drug. Given, the biomarker could be applied to the establishment of effective therapeutic strategies.